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Lipopolysaccharide‐induced increase in signalling in hippocampus is abrogated by IL‐10 – a role for IL‐1β?
Author(s) -
Lynch Aileen M.,
Walsh Christine,
Delaney Ada,
Nolan Yvonne,
Campbell Veronica A.,
Lynch Marina A.
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02157.x
Subject(s) - long term potentiation , lipopolysaccharide , hippocampal formation , hippocampus , cytokine , receptor , endocrinology , medicine , p38 mitogen activated protein kinases , inhibitory postsynaptic potential , phosphorylation , chemistry , biology , protein kinase a , microbiology and biotechnology
Parenterally administered lipopolysaccharide (LPS) increases the concentration of the pro‐inflammatory cytokine interleukin‐1β (IL‐1β) in the rat hippocampus and evidence suggests that this effect plays a significant role in inhibiting long‐term potentiation (LTP). The anti‐inflammatory cytokine IL‐10, antagonizes certain effects of IL‐1β, so if the effects of LPS are mediated through an increase in IL‐1β, it might be predicted that IL‐10 would also abrogate the effect of LPS. Here, we report that IL‐10 reversed the inhibitory effect of LPS on LTP and the data couple this with an inhibitory effect on the LPS‐induced increase in IL‐1β. LPS treatment increased hippocampal expression of IL‐1 receptor Type I protein. Consistent with the LPS‐induced increases in IL‐1β concentration and receptor expression, were downstream changes which included enhanced phosphorylation of IRAK and the stress‐activated kinases, JNK and p38; these LPS‐induced changes were reversed by IL‐10, which concurs with the idea that these events are triggered by increased activation of IL‐1RI by IL‐1β. We provide evidence which indicates that LPS treatment leads to evidence of cell death and this was reversed in hippocampus prepared from LPS‐treated rats which received IL‐10. The evidence is therefore consistent with the idea that IL‐10 acts to protect neuronal tissue from the detrimental effects induced by LPS.